Background/Aims: Emerging evidence suggests that curcumin possesses chemopreventive properties against various cancers. However, its poor bioavailability limits its clinical application. In this study, we aimed to utilize encapsulation in liposomes (Lipo) as a strategy for the clinical administration of curcumin for endometrial carcinoma (EC). Methods: Curcumin was encapsulated in a liposomal delivery system to prepare a formulation of liposomal curcumin (LC). EC cell lines Ishikawa and HEC-1 were treated with the compound and cell proliferation was measured using MTT assay. Hoechst 33258 staining assay and flow cytometry were used to detect apoptosis of the cells. Wound healing and cell invasion assays were employed to monitor cell motility. Underlying target signaling, such as NF-κB, caspases, and MMPs, were further studied via qRT-PCR and western blot. Thereafter, a zebrafish model was used to assess the toxicity of LC. Finally, a zebrafish transplantation tumor model of EC was grown and treated with LC. Tumors were monitored and harvested to study the expression of NF-κB. Results: The formation of LC was successfully developed with excellent purity and physical properties. In vitro, LC resulted in dose-dependent inhibition of proliferation, induction of apoptosis, and suppression of Ishikawa and HEC-1 cell motility. LC treatment also suppressed the activation and/or expression of NF-κB, caspase-3, and MMP-9. No demonstrable toxicity was found in the zebrafish model and tumors were suppressed after treatment with LC. PCR analysis also showed down-regulated expression of NF-κB. Conclusions: LC was successfully prepared and played biological roles against EC probably through negative regulation of the NF-κB pathway in vitro and in vivo, which demonstrates its potential therapeutic effects in EC.

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PurposeThe purpose of the study is to investigate the inhibition of hypoxia-induced angiogenesis after embolization in VX2 rabbit liver tumors by liposomal curcumin.Materials and methodsA total of 54 VX2 rabbits were divided into three groups, and each group had three subgroups according to the sacrifice time. The animals in the control group (n=18) underwent sham embolization. Transcatheter arterial embolization (TAE)-treated group (n=18) animals underwent embolization with lipiodol (0.1 mL/kg body weight) and 90–180 µm polyvinyl alcohol (PVA) particles. Liposomal curcumin TAE-treated group (n=18) animals underwent embolization with liposomal curcumin (20 mg/kg body weight) mixed with lipiodol (0.1 mL/kg body weight) and 90–180 µm PVA particles. After embolization, the animals in each subgroup were sacrificed at 6 hours, 24 hours, and 3 days, and the tumor samples were collected. Immunohistochemical staining was performed to evaluate expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) proteins, and microvessel density (MVD). Real-time polymerase chain reaction was performed to examine VEGF mRNA levels.ResultsThe levels of HIF-1α and VEGF, and MVD in tumors of liposomal curcumin TAE-treated group were significantly decreased compared to the TAE-treated group (P<0.05). There was a slight decrease in tumor size in the liposomal curcumin TAE-treated group at third-day time points compared to the TAE-treated group; the difference was not statistically significant (P>0.05). The HIF-1α protein correlated considerably with VEGF mRNA (r=0.705, P=0.001) and protein (r=0.655, P=0.003), and MVD (r=0.521, P=0.027). A significant correlation between VEGF protein and MVD was noted as well (r=0.519, P=0.027).ConclusionLiposomal curcumin downregulates HIF-1α protein levels and inhibits hypoxia-induced angiogenesis after embolization in VX2 rabbit liver tumors.

Abstracted from the nested structure of biological cells with application on the modeling of economical processes, numerical P systems (in short, NP systems) as a kind of distributed parallel computation systems have been proposed. It has been proven that NP systems and variants are Turing universal for number accepting/generating devices and language generating device. However, universality of NP systems as function computing devices has not been established. Aiming at numerical P systems with thresholds (in short, TNP systems), small universality for computing functions is discussed in this paper. Six small universal function computing devices of TNP systems for two threshold cases and working on three different modes are constructed, respectively.